crossing96/oncoscreening huggingface dataset:
Early chemotherapy discontinuation and mortality in older patients with metastatic bladder cancer: The AGEVIM multicenter cohort study.	PURPOSE: Median age for the diagnosis of metastatic bladder cancer (MBC) is 73 years. The feasibility of chemotherapy in older patients is controversial. Our objectives were to assess associations linking age to first line chemotherapy regimen selection, early chemotherapy discontinuation, and 1-year mortality in everyday practice. MATERIALS AND METHODS: Between 1999 and 2011, 197 consecutive patients aged≥70 years with MBC referred to 4 hospitals were included in the AGEVIM multicenter cohort. At baseline, we recorded performance status (PS); tumor characteristics; the Charlson Comorbidity Index; and plasma creatinine, hemoglobin, and albumin. Early discontinuation data were available for 193 patients, and overall 1-year mortality for 180 patients. We assessed the probabilities of initial cisplatin-based combination chemotherapy (CCC), early discontinuation (≤2 cycles), and 1-year mortality, using multivariate logistic regression and Cox proportional hazards modeling. RESULTS: Among the 193 patients (mean age: 76±4.3y), with 2 metastatic site in median 43.5% received CCC, 36.3% gemcitabine and carboplatin, and 20.2% gemcitabine alone. The probability of CCC decreased with age independently from sex, PS, creatinine clearance, and Charlson Comorbidity Index (P<0.0001), early discontinuation occurred in 24.9% of patients. Factors independently associated with global chemotherapy early discontinuation were age (adjusted odds ratio(per additional year) = 1.11; 95% CI: 1.02-1.20; P = 0.01) and higher metastatic-site number (adjusted odds ratio(per additional site) = 1.45; 95% CI: 1.08-1.95; P = 0.01). The number of patients was too small for a robust analysis of factors associated with early chemotherapy discontinuation in each chemotherapy regiment subgroup. Independent predictors of 1-year mortality (median = 9.6 mo) were early discontinuation (adjusted hazard ratio [aHR] = 4.77 [2.85-7.96] when PS<2 and 20.6 [9.43-44.82] when PS≥2; P<0.0001), albumin<35g/l (aHR = 3.06 [1.81-5.17], P = 0.0001), creatinine clearance<30ml/min (aHR = 2.96 [1.45-6.06], P = 0.009), and higher metastatic-site number (aHR = 1.34 [1.14-1.56], P<0.0001). CONCLUSION: Less than half of older patients with MBC received initial CCC and 25% had≤2 cycles of chemotherapy. Older age was associated with decreased CCC prescription, independently from known contraindications, and with global chemotherapy early discontinuation, but not with 1-year mortality.	bladder
The surgical management of patients with clinical stage T4 bladder cancer: A single institution experience.	INTRODUCTION: Patients with clinical T4 (cT4) bladder cancer (BCa) infrequently undergo radical cystectomy (RC). We investigated the reliability of preoperative clinical staging, perioperative and survival outcomes in patients treated with RC due to cT4a-b BCa disease at a single tertiary care institution. METHODS: The study relied on 917 BCa patients treated with RC and pelvic lymph node dissection (PLND) at a single institution between January 1995 and December 2012. We compared the accuracy of the clinical assessment with final pathology results. Moreover, we evaluated perioperative outcomes, complication rates and survival after surgery. RESULTS: The median follow-up was 62 months. Overall, 74 (8.1%) patients presented cT4 stage at preoperative evaluation. Conversely, a pathological T4 disease was confirmed only in 68.9% patients staged initially as cT4. No differences were recorded in complications, 30 days readmission or 30 days death rates between cT1-T3 vs. cT4a vs. cT4b (p > 0.1). At multivariable Cox regression analyses predicting cancer specific mortality, clinical T4 stage vs. clinical T1-2, clinical T3 stage vs. clinical T1-2 and age were predictors of worst survival after RC (all p < 0.04). CONCLUSIONS: We recorded poor concordance between preoperative imaging and pathology in cT4 patients. No differences in major perioperative outcomes and acceptable survival expectancies were reported in patients treated for cT4 disease.	bladder
Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer: A pooled individual data analysis of eight phase I-II trials.	PURPOSE: Although radical cystectomy is still considered the standard of care for most localized muscle-invasive bladder cancer (MIBC) patients, bladder-sparing strategies with chemoradiotherapy have demonstrated comparable local control and survival rates when adjusting for tumor stage. We present a pooled analysis of individual patient data out of published trials with gemcitabine-based chemoradiotherapy for MIBC. METHODS AND MATERIALS: Individual patient data were collected from Institutions that enrolled patients into trials that evaluated gemcitabine-based chemoradiotherapy for MIBC. RESULTS: We identified eight studies published on gemcitabine-based radiochemotherapy and 190 patients were included in this analysis. A complete response (CR) was observed in 166 patients (93%). After a median follow up of 44.5months, 36 patients (18.9%) presented a bladder recurrence and 14 subsequently underwent cystectomy. The 5-year overall survival (OS), disease-specific survival (DSS), and cystectomy-free survival (CFS) rates were 59%, 80.9%, and 93.3%, respectively. The achievement of CR after chemoradiotherapy was the main prognostic variable which was associated with improved OS, DSS, and CFS. The treatment was well tolerated. CONCLUSION: This pooled analysis strengthens the evidence that chemoradiotherapy regimens with concurrent gemcitabine are feasible and well tolerated. Prospective randomized controlled trials are on-going to definitively assess the efficacy of gemcitabine-based chemoradiotherapy for MIBC.	bladder
The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in the sera of bladder cancer patients.	OBJECTIVES: Studies on alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the sera of patients with malignant neoplasms show that cancer cells in many organs may release ADH isoenzymes into the blood. The aim of this study was to investigate the differences in the activity of ADH isoenzymes and ALDH in the sera of patients with bladder cancer (BCa), and with different grades of the disease. MATERIAL AND METHODS: Blood samples were taken from 39 patients with BCa (15 patients with low-grade and 24 with high-grade BCa) and from 60 healthy subjects. Class III and IV of ADH and total ADH activity were measured using the photometric method, while class I and II ADH and ALDH activity using the fluorometric method with class-specific fluorogenic substrates. RESULTS: The activity of the class I ADH isoenzyme and total ADH was significantly higher in the sera of BCa patients as compared to control group. Analysis of ALDH activity did not show statistically significant differences between the tested groups. Significantly higher total activity of ADH in comparison to control was found in both, low-grade and high-grade BCa group. The activity of ADH class I was also significantly higher in high-grade BCa group when compared to low-grade patients and controls. CONCLUSION: The increase of total ADH activity in the sera of BCa patients seems to be caused by isoenzymes released from cancerous cells. The higher activity of ADH I probably resulted from metastatic tumors as significant increase was detected only in the sera of high-grade bladder cancer patients.	bladder
RGS6 is an essential tumor suppressor that prevents bladder carcinogenesis by promoting p53 activation and DNMT1 downregulation.	Urinary bladder cancer (UBC) is largely caused by exposure to toxic chemicals including those in cigarette smoke (i.e. BBN). An activating SNP in RGS6 is associated with a pronounced reduction in UBC risk, especially among smokers. However, the mechanism underlying this reduction remains unknown. Here we demonstrate that RGS6 is robustly expressed in human urothelium, where urothelial cell carcinoma originates, and is downregulated in human UBC. Utilizing RGS6-/- mice we interrogated a possible role for RGS6 as a tumor suppressor using the BBN-induced bladder carcinogenesis model that closely recapitulates human disease. As in humans, RGS6 is robustly expressed in mouse urothelium. RGS6 loss dramatically accelerates BBN-induced bladder carcinogenesis, with RGS6-/- mice consistently displaying more advanced pathological lesions than RGS6+/+ mice. Furthermore, BBN treatment promotes urothelial RGS6 mRNA and protein downregulation. RGS6 loss impairs p53 activation and promotes aberrant accumulation of oncogenic protein DNMT1 in urothelium. Tumor suppressor RASSF1A, a DNMT1-regulated gene, is also silenced, likely via methylation of its promoter during BBN exposure. We hypothesize that this BBN-induced RGS6 loss represents a critical hit in UBC as it irrevocably impairs the anti-proliferative actions of the ATM/p53 and RASSF1A pathways. Consistent with these findings, RGS6-/- mice treated with CP-31398, a p53-stablizing agent, and/or 5-Aza, a DNMT1 inhibitor, are protected from BBN-induced tumorigenesis. Together, our data identify RGS6 as a master tumor suppressor modulating two critical signaling pathways that are often dysregulated in UBC; therefore, RGS6 represents a potential novel biomarker for UBC diagnosis/prognosis and an appealing new target in its treatment.	bladder
Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells.	In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC(50) values in a range of 8-92 μM. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.	bladder
Highly stable selenadiazole derivatives induce bladder cancer cell apoptosis and inhibit cell migration and invasion through the activation of ROS-mediated signaling pathways.	Bladder cancer is still a common malignancy of the urinary tract due to the high metastasis rate and unexpected side effects of drug treatments. The acidic environment of the urinary bladder also strongly limits the efficacy of the chemotherapeutic agents during the treatment of bladder cancer. In this study, a series of selenadiazole derivatives (SeDs) have been rationally designed and synthesized and could actively suppress the progression and metastasis of bladder cancer cells. SeDs demonstrated better antiproliferative activity and higher stability under different physiological conditions, especially in an acidic urocystic environment, than mitomycin, a clinically used anti-bladder cancer drug. In particular, compound 1b displayed better selectivity between cancer and normal cells in comparison with other compounds. Studies on the structure-activity relationship revealed that the introduction of strong electron donating substituents, such as the methoxy group, resulted in a dramatic enhancement in the anticancer efficacy. Furthermore, 1b induced anti-migration and anti-invasion activities against bladder cancer cells. Mechanistic investigation revealed that compound 1b was able to enter the cells through endocytosis and then trigger reactive oxygen species (ROS) overproduction, further causing DNA damage-mediated p53 phosphorylation and promoting cancer cell apoptosis by regulating the AKT and MAPKs signaling pathways. Altogether, the study provides a strategy for rational design of selenadiazole derivatives with improved stability to antagonize bladder cancer.	bladder
Enhancement of dendritic cells with melanoma-associated antigen 3 for inducing cytotoxicity by cytotoxic T lymphocytes on bladder cancer BIU-87 cells.	To determine the cytotoxic effect of lymphocytes activated by melanoma-associated antigen 3 (MAGE-3)-sensitized dendritic cells (DCs) on BIU-87 tumor cells, and to evaluate the possibility of MAGE-3-peptide-pulsed DCs as a vaccine in bladder cancer immunotherapy, the proliferation of T cells and the activity of cytotoxic T lymphocytes (CTLs) were examined by the MTT method. CTLs were induced by MAGE-3-sensitized DCs, or by ovalbumin (OVA) peptide and non-sensitized DCs as controls, respectively. The results indicated that MAGE-3-sensitized DCs have the ability to promote the proliferation of T cells as well as the cytotoxic activity of CTLs on bladder cancer cells in comparison with OVA peptide and non-sensitized DCs. In other words, DCs sensitized by the MAGE-3 antigen peptide could obviously upregulate the proliferation of T cells, which resulted in the growth inhibition of bladder cancer BIU-87 cells. In addition, MAGE-3-sensitized DCs played an important role in inhibiting the growth of human BIU-87 tumor xenografts in nude mice.	bladder
Sarcopenia as a Novel Preoperative Prognostic Predictor for Survival in Patients with Bladder Cancer Undergoing Radical Cystectomy.	PURPOSE: To investigate the prognostic significance of sarcopenia on long-term outcomes in patients with bladder cancer after radical cystectomy (RC). METHODS: We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma at our institution. Prognostic impact of the preoperative clinical, laboratory, and radiologic parameters were evaluated by Cox proportional hazard model analyses, and a nomogram was developed to predict cancer-specific survival (CSS) after RC. RESULTS: The mean follow-up was 46.7 months. Patients with sarcopenia had a significantly shorter CSS than those without sarcopenia. On univariate Cox analysis, clinical T stage, histology of transurethral resection of bladder tumor (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum albumin level, presence of hydronephrosis, and presence of sarcopenia were associated with significantly worse CSS. On multivariate Cox stepwise analysis, sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3; p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant independent predictors of an unfavorable prognosis Based on the results of the multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS after RC. CONCLUSIONS: Sarcopenia, clinical T stage, presence of hydronephrosis, histology of TURBT specimen, and NLR are novel preoperative prognostic factors even after adjustment for other known preoperative predictors in patients undergoing RC for bladder cancer.	bladder
Cytomorphologic and Immunophenotypic Profile of a Cohort of Small Cell Carcinoma of the Urinary Bladder.	BACKGROUND: The incidence of primary small cell carcinoma (SCC) of the urinary bladder is extremely rare. We sought to analyze the cytologic and immunophenotypic features of SCC of the urinary bladder in urine and reassert the importance of cytologic examination of urine specimens for diagnosis of this tumor. METHODS: We studied the clinical and cytomorphologic features in the presurgical urine specimens (4 voided urine and 2 bladder-washing specimens) of histopathologically and immunohistochemically proven cases of SCC of the urinary bladder. RESULTS: There were 6 cases, all males, with an age range of 61-81 years. On cytologic and histopathologic examination, typical SCC morphology was present in all cases. On immunohistochemistry, synaptophysin and CD56 were positive in all 6 cases, while chromogranin was positive in only 3. The Ki-67 labeling index ranged from 30 to 100%. CONCLUSIONS: SCC should be kept in the differential diagnosis, when high-grade urothelial carcinoma is suspected in a urine cytology specimen, as this distinction has important therapeutic and prognostic implications. Therefore, a careful observation and, if required, the use of an appropriate immunocytochemical panel on the presurgical urine specimens can lead to a correct diagnosis.	bladder
Dietary Inflammatory Index and Risk of Bladder Cancer in a Large Italian Case-control Study.	OBJECTIVE: To evaluate the association between diet in relation to its inflammatory property and bladder cancer (BC) risk. METHODS: In this study we explored the association between the dietary inflammatory index (DII) and BC risk in an Italian case-control study conducted between 2003 and 2014. Cases were 690 patients with incident and histologically confirmed BC from 4 areas in Italy. Controls were 665 cancer-free subjects admitted to the same network of hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. The DII was computed based on dietary intake assessed using a reproducible and valid 80-item food frequency questionnaire. Odds ratios (OR) were estimated through logistic regression models adjusting for age, sex, total energy intake, and other recognized confounding factors. RESULTS: Subjects in the highest quartile of DII scores (ie, with a more pro-inflammatory diet) had a higher risk of BC compared to subjects in the lowest quartile (ie, with an anti-inflammatory diet) (OR(Quartile4vs1) = 1.97; 95% [confidence interval], 1.28, 3.03; P trend = .003). Stratified analyses produced stronger associations between DII and BC risk among females (OR(Quartile4vs1) = 5.73; 95% CI = 1.46, 22.44), older ≥65 years (OR(Quartile4vs1) = 2.45; 95% CI = 1.38, 4.34), subjects with higher education ≥7 years (OR(Quartile4vs1) = 2.22; 95% CI = 1.27, 3.88), and never smokers (OR(Quartile4vs1) = 4.04; 95% CI = 1.51, 10.80). CONCLUSION: A pro-inflammatory diet as indicated by higher DII scores is associated with increased BC risk.	bladder
Risk-based Management of Non-muscle Invasive Bladder Cancer: Experience from Tribhuvan University Teaching Hospital.	Background Most of the recent evidences suggest for risk-based management of non muscle invasive bladder cancer (NMIBC) to reduce the risk of recurrence and progression. Objective This study was conducted to assess the recurrence and progression of non muscle invasive bladder cancer in Nepalese patients using European Organization for Research and Treatment of Cancer (EORTC) risk tables and to assess the effectiveness of intravesical therapy to reduce the risk of recurrence. Method A prospective observational single centre study was conducted at Tribhuvan University Teaching Hospital from January 2010- December 2012. Forty six patients with non muscle invasive bladder cancer who underwent transurethral resection of bladder tumor and completed two years follow up were included. According to the European Organization for Research and Treatment of Cancer (EORTC) risk table, the patients were divided into low, intermediate and high risk groups. The patients received postoperative adjuvant therapy and surveillance as per the European Association of Urology guidelines. Result Among the 46 patients, the overall two year recurrence and progression rate was 8 (17%) and 1 (2%) respectively. Out of seven patients in low risk category, none of them developed recurrence or progression of disease. Out of 15 patients in intermediate risk category the one year and two year recurrence rate was 13% and 20% respectively. Out of 24 patients in high risk category the one and two year recurrence rate was 17% and 21% respectively. The risk reduction by use of intravesical Bacillus Calmette Guerin (BCG) for recurrence in high risk category was 58% and 60% in first and second year respectively. In our study, the overall and individual risk group, the one and two year recurrence rate was lower than that predicted by European Organization for Research and Treatment of Cancer risk table. Conclusion Risk-based management of non muscle invasive bladder cancer by using the European Organization for Research and Treatment of Cancer risk table is a useful method of management, though its prediction rates are lower in Nepalese population.	bladder
Glucuronidation and UGT isozymes in bladder: new targets for the treatment of uroepithelial carcinomas?	Bladder cancer has been linked to numerous toxins which can be concentrated in the bladder after being absorbed into the blood and filtered by the kidneys. Excessive carcinogenic load to the bladder urothelium may result in the development of cancer. However, enzymes within the bladder can metabolize carcinogens into substrates that are safer. Importantly, these proteins, namely the UGT's (uridine 5'-diphospho-glucuronosyltransferases), have been shown to possibly prevent bladder cancer. Also, studies have shown that the UGT1 expression is decreased in uroepithelial carcinomas, which may allow for the accumulation of carcinogens in the bladder. In this review, we discuss the UGT system and its' protective role against bladder cancer, UGT genetic mutations that modulate risk from chemicals and environmental toxins, as well as targeting of the UGT enzymes by nuclear receptors.	bladder
Chronic Infections of the Urinary Tract and Bladder Cancer Risk: a Systematic Review.	Literature on the relationship between recurrent urinary tract infections and urinary bladder carcinoma risk has been inconsistent. Therefore, we carried out this systematic review of observational studies to ascertain if there is any association between chronic urinary tract infection and urinary bladder carcinoma. A total of 10 databases were searched using Boolean: CINAHL, PUBMED, Google Scholar, Medline, Science Direct, SCIRUS, Cochrane, UK PubMed central, NHS evidence and WHO-website. The search yielded an initial hit of 3,518 articles and after screening and critical appraisal, seven studies were included for this review. Four articles reported an association between chronic urinary tract infections and bladder cancer while three concluded a weak or no association at least in one gender. Main findings in this review were that most of the studies reported an association between chronic urinary tract infections and bladder cancer risk. However, inferences about the causal association between chronic urinary tract infections and bladder cancer risk should be drawn cautiously considering the methodological limitations of case-control studies included in this review. Therefore, more empirical evidence is needed to determine the causal nature of relationships between chronic urinary tract infections and bladder cancer risk.	bladder